Optimum marker selection of acute liver damage in rats in the experiment
Popov K.A., Tsymbalyuk I.Y., Sepiashvili R.I., Bykov I.M., Ustinova E.S., Bykov M.I.

Relevance. Assessment of liver damage and functional state is one of the leading tasks of clinical and laboratory diagnostics. Traditionally used methods for determining the activity of a number of indicator enzymes in blood with relative organ-specificity, such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, sorbitol dehydrogenase, alkaline phosphatase, and γ-glutamyl transferase, have low specificity for liver diseases. In this regard, the determination of the optimal marker of acute liver injury is an urgent problem. Aim. The purpose of the study is to determine the dynamics of changes in liver damage markers in rats at different periods of reperfusion after 20 minutes of ischemia in order to select the indicators that most informatively characterize the state of test-animals under conditions of correction of ischemia-reperfusion syndrome. Materials and methods: the study was performed on 120 white nonlinear male rats weighing 200–250 grams. The animals were divided into 8 groups of 15 test-animals; all of them were simulated liver ischemia by clamping the analog of the hepatoduodenal ligament with a vascular clamp for 20 minutes. Then, blood was taken from different groups of rats at different reperfusion times – 5, 15, 30, 60, 120, 180 minutes, 8 hours and a day. In the blood plasma of laboratory animals, the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutathione transferase (GST), and lactate concentration were determined. Results: the results obtained allowed us to characterize two main peaks of indicators: a 5-minute period after restoration of blood flow – the maximum activity of glutathione transferase and lactate concentration, increased by 3.9–4.7 times; 60–180 minutes of reperfusion is the peak of aminotransferase activity, a significant increase in the activity of which begins 60 minutes after the restoration of blood flow and reaches its maximum by the 3rd hour of reperfusion, and LDH, the peak of which is recorded already by the 60th minute of revascularization. At the same time, after 8 hours of reperfusion, an obvious tendency for a decrease in all studied parameters was determined, which ends a day after modeling ischemia with a decrease to the level of control values. Conclusion: the assessment of organ damage in the ischemic period and the anti-ischemic effect of metabolic drugs can be carried out with the determination of an increase in lactate concentration and glutathione transferase activity almost immediately after restoration of blood flow. The development of injuries during the reperfusion period is more expedient to assess by determining AST, ALT and LDH after a 3-hour period of blood flow restoration, at which time the maximum values of markers are recorded under the condition of 20-minute total liver ischemia.

RUDN Journal of Medicine. 2020;24(4):293-303
Regulatory cytokine effects in vitro on the phenotype of subpopulations CD62L+CD63-, CD62L+CD63+ and microbicidal activity of neutrophilic granulocytes in patients with colorectal cancer
Chudilova G.A., Nesterova I.V., Kovaleva S.V., Lomtatidze L.V.

Relevance. Neutrophilic granulocytes (NG) are the first cells of the immune system to migrate to the tumor and are actively involved in the implementation of a full-fledged antitumor response through the mechanisms of direct killing of tumor cells, extracellular lysis (NET), and through the activation of antibody-dependent cellular cytotoxicity (ADCC), inhibition of angiogenesis, initiation of other cells with antitumor activity. The aim of the study was to study the effect of cytokines IFNα, IFNγ, G-CSF on the CD62L+CD63- and CD62L+CD63+ subsets and the microbicidal activity of NGs in patients with colorectal cancer (CRC) in vitro. Materials and methods. We studied samples of peripheral blood (PB) of 10 patients of both sexes 38-70 years old with newly diagnosed untreated CRC stage II-III (study group) and 10 healthy volunteers (comparison group). The subsets CD62L+CD63+ NG, CD62L+CD63- NG were assessed by flow cytometry (CYTOMICS FC500, Beckman Coulter, USA), the microbicidal functions of NG were tested by cytochemical methods: activity of NADPH - oxidases, myeloperoxidase (MP), level of cationic protein (CP) in spontaneous tests and under additional stress of S. aureus . The effect of IFNα, IFNγ, G-CSF cytokines on subsets and the microbicidal activity of NG in vitro was studied in both study groups. Microsoft Exel 2016 and StatPlus 2010 were used for statistical processing of the obtained data using nonparametric tests: Me (Q1; Q3), Mann-Whitney U-test and Wilcoxon test . Results . The features of transformation of CD62L+ CD63-NG and CD62L+ CD63+ NG subsets of PB in CRC have been established, that allows to get an idea of the NG ability to roll and readiness to activate the microbicidal arsenal, various defects of spontaneous and induced microbicidal activity of oxygendependent and oxygen-independent mechanisms of NG. The effects of cytokine influence on NG in CRC in vitro have been shown, which indicates the possibility of regulating the receptor and microbicidal functions of NG, and, on the other hand, suggests defects in NG perception of regulatory stimuli, that is confirmed by the progression of tumor growth.

RUDN Journal of Medicine. 2020;24(4):304-314
Complex effect of caffeine and dioxidine on behavioral responses in mice in Porsolt test
Durnova N.A., Karetnikova A.Y., Isaev D.S., Klantsataya A.R., Sheremetyeva A.S.

Relevance. In light of the popularization of the use of caffeine-containing products, the question of the combined use of caffeine with substances exhibiting a toxic effect remains open. The doses of caffeine, which have a pronounced antidepressant effect, are also insufficiently studied. The aim of the study was to study the effect of repeated administration of caffeine and dioxidine on the behavioral responses of mice in the Porsolt test. Materials and methods. The experiment was carried out on 36 outbred male mice, divided into 6 groups. Experimental groups for 15 days of the study received caffeine at a dose of 40 mg/kg (first) or 100 mg/kg (second), dioxidine at a dose of 200 mg/kg (third), together with caffeine 40 mg/kg or 100 mg/kg, and dioxidine (fourth and fifth groups, respectively). The animals of the control group were injected with saline. To study the behavior, the Porsolt test was carried out, evaluating the following indicators on the 1st, 8th and 15th days of the experiment: the total time of immobilization, active swimming, climb, the number of grooming and shaking off acts. Results . The administration of caffeine at a dose of 40 mg/kg caused an increase in the time of active swimming and a decrease in the duration of immobilization on the 8th and 15th days. When caffeine was used at a dose of 100 mg/kg, an increase in the time of active swimming was noted with a single exposure, with an experiment duration of 8-15 days, an increase in the duration of immobilization was observed. Dioxidine caused a significant decrease in the time of active swimming and an increase in the duration of immobilization during all days of the experiment. The combined use of caffeine (40 mg/kg and 100 mg/kg) and dioxidine on the 1st day led to a decrease in immobilization and the time of active swimming. In both groups, 100 % animal mortality was observed by the 15th day. Conclusion. The results of the study indicate the presence of an antidepressant effect in caffeine at a dose of 40 mg/kg on the 8th and 15th days of the experiment and the absence of this effect in caffeine at a dose of 100 mg/kg with a duration of administration of 8-15 days. The use of dioxidine led to the absence of antidepressant activity and the presence of the opposite effect. The combined administration of caffeine (40 mg/kg and 100 mg/kg) and dioxidine led to 100 % mortality in the experimental groups by the 15th day of the experiment

RUDN Journal of Medicine. 2020;24(4):315-324
Ceramids as biomarkers of chronic periodontitis associated with type 2 diabetes
Unanyan K.G., Balmasova I.P., Tsarev V.N., Mkrtumyan A.M., Elbekyan K.S., Karakov K.G., Arutyunov S.D.

Relevance . The association of chronic periodontitis with type 2 diabetes mellitus is one of the most frequent manifestations of systemic effects that are etiologically associated with periodontopathogenic bacteria in the biofilm of the gingival sulcus. In this regard, the study of the metabolic mechanisms leading to such systemic effects and serving their markers is an urgent problem. Aim . Study of the features of sphingolipid/ceramide metabolism, both produced by etiologically significant microflora, and present in periodontal tissues of patients on the example of the association of chronic periodontitis with type 2 diabetes. Materials and methods . The observation groups included 58 patients with chronic periodontitis in association with type 2 diabetes, 39 patients with chronic periodontitis without concomitant systemic pathology, and 27 conditionally healthy people. All the examined patients underwent molecular genetic studies of the taxonomic and metabolic profiles of the dental sulcus/ periodontal pockets microbiota using 16S sequencing and evaluation of phosphorylated ceramides in saliva by the activity of the ceramid kinase enzyme. Results . It was found that in the Association of chronic periodontitis with type 2 diabetes mellitus, there are features of the taxonomic composition of the dental sulcus/periodontal pockets microbiota, which are combined with a decrease in sphingolipid metabolism. In addition, in these patients, depending on the duration of diabetes mellitus, there was an increasing drop in the saliva of ceramide kinase, which determines the phosphorylation of sphingolipids/ceramides. Conclusion . In the Association of chronic periodontitis with type 2 diabetes mellitus, the systemic effects of the dental sulcus/ periodontal pockets microbiota are manifested by a decrease in sphingolipid metabolism, including a decrease in ceramide kinase in periodontal tissues, which can serve as a marker of the combined pathological process.

RUDN Journal of Medicine. 2020;24(4):325-337
Effect of supraspinal influences on the manifestation of presynaptic inhibition Ia afferents in different types of muscle contraction in humans
Bogdanov S.M., Gladchenko D.A., Roshchina L.V., Chelnokov A.A.

Relevance. Тhe biological role of presynaptic inhibition is to regulate excessive skeletal muscle tone, which prevents the execution of arbitrary muscle contractions. In the modern literature, there is information devoted mainly to the study of various types of spinal inhibition in the isometric type of contraction. The aim: determining the role of supraspinal influences from brain stem structures on the activity of presynaptic inhibition when performing various types and sizes of muscle contractions in humans. Materials and methods: 20-22 year-old healthy men (n=6) took part in the research. Presynaptic inhibition was registered at rest; at rest in combination with the performance of Jendrassik maneuver; when performing concentric, eccentric, isometric contractions of 50 % and 100 % of the individual maximum without and against the background of Jendrassik maneuver. Results: During the execution of concentric, eccentric and isometric contractions of different sizes, the severity of presynaptic inhibition decreases in comparison with rest, both without taking Jendrassik maneuver, and against the background of its execution. With an increase in the strength of concentric, eccentric, and isometric contractions from 50 % to 100 % of the individual maximum, the severity of presynaptic inhibition progressively decreased under the same experimental conditions. Without taking Jendrassik maneuver, the greatest severity of presynaptic inhibition was observed with concentric and isometric contractions of 50 % and 100 % of the MVC, and against the background of taking Jendrassik maneuver - with an isometric type of reduction of 50 % and 100 % of the MVC. Conclusion. Supraspinal descending effects caused by the Jendrassik maneuver modulate the state of presynaptic inhibition Ia of the afferents of the flexor muscle of the foot, depending on the type and strength of muscle contraction.

RUDN Journal of Medicine. 2020;24(4):338-344
Typological features of the brain in normal conditions and in cerebral hypoperfusion
Chrishtop V.V., Rumyantseva T.A., Nikonorova V.G.

Relevance. Stress resistance and cognitive abilities of the patient, forming the personal component of the rehabilitation potential, have a significant impact on the course and recovery period after cerebral hypoxia of various origins. The adaptation of rehabilitation measures to the individual characteristics of the patient will significantly increase the effectiveness of rehabilitation measures for stroke and neurodegenerative diseases. The aim of this work is to generalize experimental and clinical studies characterizing the influence of individual characteristics of higher nervous activity on the course of cerebral hypoperfusion. Materials and methods . The study of literary sources of scientometric scientific bases for the last 15 years has been carried out. Results . The level of stress resistance is based on alternative biochemical strategies of neuronal metabolism of macroergs and neurotransmitters. At the organismic level, this is realized in a greater base voltage of the stress-activating system and a smaller reserve capacity of the sympathoadrenal system. In general, this leads to more severe cerebral hypoperfusion in stress-resistant individuals and slower recovery and is correlated with a high baseline sympathetic nervous system tone, insulin and testosterone concentrations. At the same time, a low level of stress resistance determines a greater sensitivity to exogenous corrective influences in cerebral hypoperfusion. The level of cognitive ability is associated with astrocytic responses and the organization of synaptic ensembles. The participation of astrocytes in the regulation of glutamate levels probably has a combined effect on both the state of cognitive mechanisms and damage to the components of neuroglial assemblies during hypoxia. This is also due to the release of S100β +, which, in turn, enhances the coordinated oscillations of neurons in the medial prefrontal cortex and hippocampus and may be the cause of greater damage to the cells of the cerebral hemispheres of the brain in animals with a high level of cognitive abilities in the cerebral hypoperfusion model.

RUDN Journal of Medicine. 2020;24(4):345-353
Immunopathogenetically reasonable program effectiveness of systemic and local interferonotherapy in immunocompromised young children
Nesterova I.V., Kovaleva S.V., Khalturina E.O., Chudilova G.A.

Relevance. In recent years, there has been a steady increase in the incidence of children morbidity, in the structure of which infectious pathology occupies a leading position. The development of «minimal persistent inflammation» of the upper respiratory tract mucosa is the basis for the persistence of microflora, the entrance gate for allergens and irritants, and creates conditions for the timing of the inflammation. The aim of the study: based on the study of the features of the immune system and interferon system in immunocompromised children of early age suffering from co-infections: return ARVI associated with atypical chronic herpes virus infections, to develop a new program of local and systemic interferon therapy and evaluate its effectiveness. Materials and methods: We observed 30 children aged 1-4 years, 16 boys and 14 girls suffering from recurrent ARVI associated with various atypical chronic active herpes virus infections (ACHA-HVI) (HSV I/II, EBV, CMV, HHV VI). The comparison group was 20 conditionally healthy children, comparable by sex and age. We used clinical and immunological methods: ELISA, PCR, cytofluorimetry. Results: A clinical and anamnestic investigation showed that young children had clinical features of immunocomprometization: a high rate of recurrent ARVI of 10-15 or more episodes per year, and the duration of these episodes ranged from 7 to 12 days, while in 100 % of cases there were recurrent monoand/or mixed ACHA-HVI. A study of the state of the immune system and the interferon system showed that children of the study group were deficient in T cytotoxic lymphocytes, natural killer cells, serum IFNα, serum IgA, and various disorders of neutrophil granulocytes (NG). A new immunopathogenetically based program of local and systemic therapy with recombinant IFNα2b in combination with antioxidants has been developed. This program demonstrated a high clinical-immunological effectiveness, providing in a significant reduction of ARVI episode rates, a reduction in the duration of IRVI, as well as the number of complicated ARVI, a decrease in the replicative activity of herpes viruses in a field of restoration of the interferon system, a significant improvement of antiviral and antibacterial immune response. Conclusions: A new immunopathogenetically based program of systemic and local IFNtherapy for immunocompromised young children has been created. The high clinical-immunological effectiveness and immunoprophylactic orientation of the developed local and systemic program of interferonotherapy have been demonstrated.

RUDN Journal of Medicine. 2020;24(4):354-367
Pseudopelade of Brock: clinical observation
Ryabov S.K., Mesnyankina O.A.

The article presents clinical observation of a rare variant of scarring alopecia - pseudopelade Brock. The presented case demonstrates the important role of detailed examination and close attention to patients with long-term foci of hair loss in the absence of positive dynamics from the therapy, maintaining clinical alertness and conducting a broad differential diagnostic search to exclude rare dermatoses, and also confirms the need for histological examination of skin biopsies to verify the diagnosis.

RUDN Journal of Medicine. 2020;24(4):368-372

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